Y-3 pharmaceutical composition for injection and preparation method thereof

Abstract

The invention provides a pharmaceutical composition and a preparation method thereof. The pharmaceutical composition comprises Y-3, hydroxypropyl-beta-cyclodextrin, mannitol, Tween 80 and the like. The Y-3 pharmaceutical composition for injection provided by the invention is high in solubility, good in stability and few in free drugs, and can effectively improve patient compliance and medication safety.

Description

Technical Field

[0003] The invention belongs to the technical field of medicines and relates to a Y-3 pharmaceutical composition for injection and a preparation method thereof. Background Art

[0005] Y-3 injection is a new structural small molecule neuroprotectant developed by Nanjing Ningdan New Drug Technology Co., Ltd. with independent intellectual property rights. Its active ingredient Y-3 has dual-target activity of dissociating PSD-95 and nNOS coupling and exciting α2-GABAAR. In cerebral ischemic injury, Y-3 intervenes in the dual targets of PSD95-nNOS and α2-GABAAR at the same time, which is more conducive to exerting brain protection; at the same time, as a positive allosteric regulator of α2-GABAAR, it eliminates the GABA disinhibition effect of the NMDAR-PSD-95-nNOS signaling pathway, which is conducive to maintaining the efficacy of the drug.

[0006] Y-3 can selectively act on pathological NMDAR downstream targets, that is, it only inhibits the PSD-95-nNOS coupling induced by cerebral ischemia, and does not affect the coupling of the two proteins under physiological conditions and other related protein-protein interactions and protein expressions downstream of the NMDA receptor. In addition, since Y-3 selectively excites α2-GABAAR and has no effect on the α1 subtype, it can reduce various adverse central nervous system effects mediated by the α1 subtype of GABAAR during use, including sedation, ataxia, amnesia, tolerance and addiction.

[0007]

[0008] WO2013064031A1 discloses a class of N-benzylaniline derivatives. The most prominent feature of this class of drugs is that they have protective effects on cerebral ischemia-reperfusion injury and analgesic effects on chronic pathological pain. They can be used to prepare drugs for treating stroke, neuropathic pain, and inflammatory pathological pain.

[0009] CN116407530A discloses a composition, a Y-3 micellar injection and a preparation method thereof, comprising Y-3, propylene glycol and 15-hydroxystearate polyethylene glycol, and provides a preparation method of the Y-3 micellar injection and an application thereof.

[0010] Due to the physicochemical properties of Y-3 API, it is classified as BCS IV in biopharmaceutics, which is a poorly soluble and poorly permeable drug. It is difficult to prepare oral drugs in the prior art, and conventional injection prescriptions cannot meet the solubility required for the dosage. Therefore, clinical research urgently needs a Y-3 injection that can meet the solubility requirements and achieve a stable formulation that meets clinical needs.

[0011] Hydroxypropyl-β-cyclodextrin is a widely used modified cyclodextrin, which is formed by 7 glucose units to form a lipophilic cavity. After the drug is complexed with hydroxypropyl-β-cyclodextrin, its water solubility will be greatly enhanced. Hydroxypropyl-β-cyclodextrin has good solubility in water and has a certain relative hygroscopicity. It is non-irritating to muscles and is an ideal solubilizer and drug excipient for injections. It can improve the water solubility of poorly soluble drugs, increase drug stability, improve drug bioavailability, increase the efficacy of drugs or reduce the dosage, adjust or control the release rate of drugs, and reduce drug toxicity and side effects. Summary of the invention

[0013] The technical problem solved by the present invention is to provide a composition. The Y-3 pharmaceutical composition for injection provided in the present application can improve the solubility of Y-3 and has a high encapsulation rate, thereby effectively alleviating the pain of patients and improving compliance.

[0014] The present application provides a Y-3 pharmaceutical composition for injection, which includes Y-3, hydroxypropyl-β-cyclodextrin, mannitol and Tween 80. The present application adopts hydroxypropyl-β-cyclodextrin and Tween 80 in combination, which can effectively improve the solubility of Y-3, has good stability, has less free drugs, and can effectively improve patient compliance and medication safety. DETAILED DESCRIPTION

[0016] In order to further understand the present invention, preferred embodiments of the present invention are described below in conjunction with examples. However, it should be understood that these descriptions are only for further illustrating the features and advantages of the present invention, rather than limiting the claims of the present invention.

[0017] In view of the problem that Y-3 is difficult to dissolve and penetrate in the prior art, the present application provides a Y-3 pharmaceutical composition for injection, which uses hydroxypropyl-β-cyclodextrin and Tween 80 as solubilizing excipients and mannitol as a lyophilization protective agent. In addition to improving the solubility of Y-3, it can also improve the encapsulation rate, reduce the free drug concentration of Y-3, and improve patient compliance and medication safety. Specifically, an embodiment of the present invention discloses a composition, including Y-3, hydroxypropyl-β-cyclodextrin, mannitol and Tween 80.

[0018] In the composition provided in the present application, Y-3 is used as an active ingredient, hydroxypropyl-β-cyclodextrin and Tween 80 are used as solubilizing excipients, and mannitol is used as a lyophilization protective agent, which can effectively improve the solubility of Y-3.

[0019] Further, the content of Y-3 is 0.1~10 mg / ml, the content of hydroxypropyl-β-cyclodextrin is 1~60wt%, the content of mannitol is 0.1~10 wt%, and the content of Tween 80 is 0.01~2 wt%; more specifically, the content of Y-3 is 0.1~10 mg / ml, the content of hydroxypropyl-β-cyclodextrin is 10~50 wt%, the content of mannitol is 1~7 wt%, and the content of Tween 80 is 0.1~1 wt%.

[0020] The present application also provides a Y-3 pharmaceutical composition for injection, comprising Y-3, hydroxypropyl-β-cyclodextrin, mannitol, Tween 80 and a solvent.

[0021] In the Y-3 pharmaceutical composition for injection described in the present application, the solvent is selected from water for injection.

[0022] The Y-3 pharmaceutical composition for injection also includes a pharmaceutically acceptable excipient, which may be a pH regulator, which may be hydrochloric acid or sodium hydroxide, or a lyophilizing protective agent, which may be mannitol or sorbitol.

[0023] In the Y-3 pharmaceutical composition for injection, if the content of hydroxypropyl-β-cyclodextrin and Tween 80 is too much, the injection solution will have safety problems. If the content of hydroxypropyl-β-cyclodextrin and Tween 80 is too little, there will be solubility problems and the raw material Y-3 will precipitate.

[0024] The present application also provides a method for preparing a Y-3 pharmaceutical composition for injection, comprising:

[0025] Dissolve hydroxypropyl-β-cyclodextrin in a solvent, add Tween 80 and mannitol, add Y-3 after the solution becomes clear, stir or high shear to dissolve it, adjust the pH, add water for injection, filter, fill, and freeze-dry to obtain a Y-3 pharmaceutical composition for injection.

[0026] Specifically, the preparation method of the Y-3 pharmaceutical composition for injection comprises the following steps:

[0027] First, weigh Tween 80, add water for injection, and prepare to the required concentration. Then weigh hydroxypropyl-β-cyclodextrin, add water for injection, add the prepared Tween 80, stir to dissolve it, then add Y-3, adjust the pH, add water for injection, filter, fill, and freeze-dry to obtain the Y-3 pharmaceutical composition for injection.

[0028] The encapsulation rate of the Y-3 pharmaceutical composition for injection of the present application is >90%, and more specifically, the encapsulation rate of the Y-3 pharmaceutical composition for injection is >95%.

[0029] The Y-3 pharmaceutical composition for injection provided by the present application can effectively improve the solubility of Y-3 by adopting a variety of conventional excipients with high safety; improve patient compliance and medication safety; and the preparation process of the Y-3 pharmaceutical composition for injection is simple, which improves the stability of Y-3.

[0030] In order to further understand the present invention, the composition, the Y-3 pharmaceutical composition for injection and the preparation method thereof provided by the present invention are described in detail below in conjunction with the examples. The protection scope of the present invention is not limited by the following examples.

[0031] The invention discloses Y-3 pharmaceutical composition for injection, and those skilled in the art can learn from the content of the present invention, combine the principles of pharmaceutics, and appropriately improve the process parameters or the prescription ratio to realize. It is particularly important to point out that all similar replacements and modifications are obvious to those skilled in the art, and they are all considered to be included within the scope of the invention. Application of the present invention has been described by preferred embodiments, and relevant personnel can obviously change or appropriately change and combine the methods and applications described herein without departing from the content, spirit and scope of the present invention, to realize and apply the technology of the present invention.

[0032] Y-3 mentioned in the examples is (1R,2S,4R)-1,7,7-trimethyl-bicyclo[2.2.1]hept-2-yl-4-((3,5-dichloro-2-hydroxybenzyl)amino)-2-hydroxybenzoate.

[0033] Example 1

[0034] The Y-3 pharmaceutical composition for injection in this example is prepared according to the ingredients in Table 1:

[0035] Table 1 Ingredients of the Y-3 pharmaceutical composition for injection provided in Example 1

[0036] Element prescription Y-3 50 mg Hydroxypropyl-β-cyclodextrin 10 g Water for injection 90 g

[0037] Preparation method: Weigh hydroxypropyl-β-cyclodextrin, add water for injection, stir to dissolve, then add Y-3, high shear, adjust pH, add water for injection, fill, freeze-dry, and obtain the Y-3 pharmaceutical composition for injection.

[0038] Example 2

[0039] The Y-3 pharmaceutical composition for injection in this example is prepared according to the ingredients in Table 2:

[0040] Table 2 Ingredients of the Y-3 pharmaceutical composition for injection provided in Example 2

[0041] Element prescription Y-3 50 mg Hydroxypropyl-β-cyclodextrin 15 g Water for injection 85 g

[0042] Preparation method: Weigh hydroxypropyl-β-cyclodextrin, add water for injection, stir to dissolve, then add Y-3, high shear, adjust pH, add water for injection, fill, freeze-dry, and obtain the Y-3 pharmaceutical composition for injection.

[0043] Example 3

[0044] The Y-3 pharmaceutical composition for injection in this example is prepared according to the ingredients in Table 3:

[0045] Table 3 Ingredients of the Y-3 pharmaceutical composition for injection provided in Example 3

[0046] Element prescription Y-3 100 mg Hydroxypropyl-β-cyclodextrin 30 g Water for injection 70 g

[0047] Preparation method: Weigh hydroxypropyl-β-cyclodextrin, add water for injection, stir to dissolve, then add Y-3, high shear, adjust pH, add water for injection, fill, freeze-dry, and obtain the Y-3 pharmaceutical composition for injection.

[0048] Example 4

[0049] The Y-3 pharmaceutical composition for injection in this example is prepared according to the ingredients in Table 4:

[0050] Table 4 Ingredients of the Y-3 pharmaceutical composition for injection provided in Example 4

[0051] Element prescription Y-3 50 mg Hydroxypropyl-β-cyclodextrin 15 g Tween 80 1 g Water for injection 84 g

[0052] Preparation method: Weigh hydroxypropyl-β-cyclodextrin and Tween 80, add water for injection, stir to dissolve, then add Y-3, high shear, adjust pH, add water for injection, fill, freeze-dry, and obtain the Y-3 pharmaceutical composition for injection.

[0053] Example 5

[0054] The Y-3 pharmaceutical composition for injection in this example is prepared according to the ingredients in Table 5:

[0055] Table 5 Ingredients of the Y-3 pharmaceutical composition for injection provided in Example 5

[0056] Element prescription Y-3 200 mg Hydroxypropyl-β-cyclodextrin 30 g Tween 80 1 g Water for injection 69 g

[0057] Preparation method: Weigh hydroxypropyl-β-cyclodextrin and Tween 80, add water for injection, stir to dissolve, then add Y-3, high shear, adjust pH, add water for injection, fill, freeze-dry, and obtain the Y-3 pharmaceutical composition for injection.

[0058] Example 6

[0059] The Y-3 pharmaceutical composition for injection in this example is prepared according to the ingredients in Table 6:

[0060] Table 6 Ingredients of the Y-3 pharmaceutical composition for injection provided in Example 6

[0061] Element prescription Y-3 400 mg Hydroxypropyl-β-cyclodextrin 35 g Tween 80 0.1 g Water for injection 64.9 g

[0062] Preparation method: Weigh hydroxypropyl-β-cyclodextrin and Tween 80, add water for injection, stir to dissolve, then add Y-3, high shear, adjust pH, add water for injection, fill, freeze-dry, and obtain the Y-3 pharmaceutical composition for injection.

[0063] Example 7

[0064] The Y-3 pharmaceutical composition for injection in this example is prepared according to the ingredients in Table 7:

[0065] Table 7 Ingredients of the Y-3 pharmaceutical composition for injection provided in Example 7

[0066] Element prescription Y-3 400 mg Hydroxypropyl-β-cyclodextrin 35 g Tween 80 0.3 g Water for injection 64.7 g

[0067] Preparation method: Weigh hydroxypropyl-β-cyclodextrin and Tween 80, add water for injection, stir to dissolve, then add Y-3, high shear, adjust pH, add water for injection, fill, freeze-dry, and obtain the Y-3 pharmaceutical composition for injection.

[0068] Example 8

[0069] The Y-3 pharmaceutical composition for injection in this example is prepared according to the ingredients in Table 8:

[0070] Table 8 Ingredients of the Y-3 pharmaceutical composition for injection provided in Example 8

[0071] Element prescription Y-3 400 mg Hydroxypropyl-β-cyclodextrin 35 g Tween 80 0.5 g Water for injection 64.5 g

[0072] Preparation method: Weigh hydroxypropyl-β-cyclodextrin and Tween 80, add water for injection, stir to dissolve, then add Y-3, high shear, adjust pH, add water for injection, fill, freeze-dry, and obtain the Y-3 pharmaceutical composition for injection.

[0073] Example 9

[0074] The Y-3 pharmaceutical composition for injection in this example is prepared according to the ingredients in Table 9:

[0075] Table 9 Ingredients of the Y-3 pharmaceutical composition for injection provided in Example 9

[0076] Element prescription Y-3 400 mg Hydroxypropyl-β-cyclodextrin 35 g Tween 80 1 g Water for injection 64 g

[0077] Preparation method: Weigh hydroxypropyl-β-cyclodextrin and Tween 80, add water for injection, stir to dissolve, then add Y-3, high shear, adjust pH, add water for injection, fill, freeze-dry, and obtain the Y-3 pharmaceutical composition for injection.

[0078] Example 10

[0079] The Y-3 pharmaceutical composition for injection in this example is prepared according to the ingredients in Table 10:

[0080] Table 10 Ingredients of the Y-3 pharmaceutical composition for injection provided in Example 10

[0081] Element prescription Y-3 400 mg Hydroxypropyl-β-cyclodextrin 40 g Tween 80 0.1 g Water for injection 59.9 g

[0082] Preparation method: Weigh hydroxypropyl-β-cyclodextrin and Tween 80, add water for injection, stir to dissolve, then add Y-3, high shear, adjust pH, add water for injection, fill, freeze-dry, and obtain the Y-3 pharmaceutical composition for injection.

[0083] Embodiment 11

[0084] The Y-3 pharmaceutical composition for injection in this example is prepared according to the ingredients in Table 11:

[0085] Table 11 Ingredients of the Y-3 pharmaceutical composition for injection provided in Example 11

[0086] Element prescription Y-3 400 mg Hydroxypropyl-β-cyclodextrin 40 g Tween 80 0.3 g Water for injection 59.7 g

[0087] Preparation method: Weigh hydroxypropyl-β-cyclodextrin and Tween 80, add water for injection, stir to dissolve, then add Y-3, high shear, adjust pH, add water for injection, fill, freeze-dry, and obtain the Y-3 pharmaceutical composition for injection.

[0088] Example 12

[0089] The Y-3 pharmaceutical composition for injection in this example is prepared according to the ingredients in Table 12:

[0090] Table 12 Ingredients of the Y-3 pharmaceutical composition for injection provided in Example 12

[0091] Element prescription Y-3 500 mg Hydroxypropyl-β-cyclodextrin 40 g Tween 80 0.5 g Water for injection 59.5 g

[0092] Preparation method: Weigh hydroxypropyl-β-cyclodextrin and Tween 80, add water for injection, stir to dissolve, then add Y-3, high shear, adjust pH, add water for injection, fill, freeze-dry, and obtain the Y-3 pharmaceutical composition for injection.

[0093] Embodiment 13

[0094] The Y-3 pharmaceutical composition for injection in this example is prepared according to the ingredients in Table 13:

[0095] Table 13 Ingredients of the Y-3 pharmaceutical composition for injection provided in Example 13

[0096] Element prescription Y-3 600 mg Hydroxypropyl-β-cyclodextrin 40 g Tween 80 1 g Water for injection 59 g

[0097] Preparation method: Weigh hydroxypropyl-β-cyclodextrin and Tween 80, add water for injection, stir to dissolve, then add Y-3, high shear, adjust pH, add water for injection, fill, freeze-dry, and obtain the Y-3 pharmaceutical composition for injection.

[0098] Embodiment 14

[0099] The Y-3 pharmaceutical composition for injection in this example is prepared according to the ingredients in Table 14:

[0100] Table 14 Ingredients of the Y-3 pharmaceutical composition for injection provided in Example 14

[0101] Element prescription Y-3 600 mg Hydroxypropyl-β-cyclodextrin 45 g Tween 80 0.5 g Water for injection 54.5 g

[0102] Preparation method: Weigh hydroxypropyl-β-cyclodextrin and Tween 80, add water for injection, stir to dissolve, then add Y-3, high shear, adjust pH, add water for injection, fill, freeze-dry, and obtain the Y-3 pharmaceutical composition for injection.

[0103] Embodiment 15

[0104] The Y-3 pharmaceutical composition for injection in this example is prepared according to the ingredients in Table 15:

[0105] Table 15 Ingredients of the Y-3 pharmaceutical composition for injection provided in Example 15

[0106] Element prescription Y-3 600 mg Hydroxypropyl-β-cyclodextrin 45 g Tween 80 1 g Water for injection 54 g

[0107] Preparation method: Weigh hydroxypropyl-β-cyclodextrin and Tween 80, add water for injection, stir to dissolve, then add Y-3, high shear, adjust pH, add water for injection, fill, freeze-dry, and obtain the Y-3 pharmaceutical composition for injection.

[0108] Example 16

[0109] The Y-3 pharmaceutical composition for injection in this example is prepared according to the ingredients in Table 16:

[0110] Table 16 Ingredients of the Y-3 pharmaceutical composition for injection provided in Example 16

[0111] Element prescription Y-3 600 mg Hydroxypropyl-β-cyclodextrin 50 g Tween 80 0.5 g Water for injection 49.5 g

[0112] Preparation method: Weigh hydroxypropyl-β-cyclodextrin and Tween 80, add water for injection, stir to dissolve, then add Y-3, high shear, adjust pH, add water for injection, fill, freeze-dry, and obtain the Y-3 pharmaceutical composition for injection.

[0113] Embodiment 17

[0114] The Y-3 pharmaceutical composition for injection in this example is prepared according to the ingredients in Table 17:

[0115] Table 17 Ingredients of the Y-3 pharmaceutical composition for injection provided in Example 17

[0116] Element prescription Y-3 445.15 mg Hydroxypropyl-β-cyclodextrin 35 g Mannitol 2.5 g Tween 80 0.01 g Water for injection 62.49 g

[0117] Preparation method: Weigh hydroxypropyl-β-cyclodextrin, Tween 80, and mannitol, add water for injection, stir to dissolve, then add Y-3, high shear, adjust pH, add water for injection, filter, fill, and freeze-dry to obtain the Y-3 pharmaceutical composition for injection.

[0118] Embodiment 18

[0119] The Y-3 pharmaceutical composition for injection in this example is prepared according to the ingredients in Table 18:

[0120] Table 18 Ingredients of the Y-3 pharmaceutical composition for injection provided in Example 18

[0121] Element prescription Y-3 445.15 mg Hydroxypropyl-β-cyclodextrin 35 g Sorbitol 5 g Tween 80 0.01 g Water for injection 57.49 g

[0122] Preparation method: Weigh hydroxypropyl-β-cyclodextrin, Tween 80, and sorbitol, add water for injection, stir to dissolve, then add Y-3, high shear, adjust pH, add water for injection, filter, fill, and freeze-dry to obtain the Y-3 pharmaceutical composition for injection.

[0123] Embodiment 19

[0124] The contents of the preparation solutions obtained in Examples 1-18 and related substances were detected by high performance liquid chromatography, and the test results are shown in Table 19;

[0125] Table 19 Data table of content and related substance detection results of Examples 1 to 18

[0126] Example Content (mg / ml) Related substances (%) Example 1 0.48 2.14 Example 2 0.49 1.98 Example 3 1.02 1.23 Example 4 0.50 1.65 Example 5 2.01 1.75 Example 6 3.97 1.62 Example 7 3.85 1.34 Example 8 3.96 1.21 Example 9 3.99 1.33 Example 10 4.01 1.41 Embodiment 11 4.01 1.56 Example 12 5.00 0.92 Embodiment 13 6.01 0.88 Embodiment 14 5.97 0.76 Embodiment 15 5.99 0.82 Example 16 6.01 0.93 Embodiment 17 4.44 0.85 Embodiment 18 4.39 0.79

[0127] The above data show that the combination of hydroxypropyl-β-cyclodextrin and Tween 80 used in the example can effectively improve the solubility of Y-3, while significantly reducing related substances.

[0128] Example 20 Redissolution time detection

[0129] The re-dissolution time of Examples 1-18 was tested, and the test results are shown in Table 20

[0130] Table 20 Data table of re-dissolution time test results of Examples 1-18

[0131] Example Reconstitution time Example 1 1 minute 40 seconds Example 2 2 minutes 46 seconds 3 2 minutes 42 seconds 4 2 minutes 46 seconds 5 3 minutes 40 seconds 6 3 minutes 26 seconds 7 2 minutes 40 seconds 8 2 minutes 46 seconds 9 1 minute 47 seconds 10 1 minute 42 seconds 11 1 minute 40 seconds 12 2 minutes 49 seconds 13 2 minutes 55 seconds 14 3 minutes 18 seconds 15 3 minutes 40 seconds 16 3 minutes 56 seconds 17 2 minutes 32 seconds 18 2 minutes 56 seconds

[0132] The above data show that Examples 1-18 all have good re-dissolution effects.

[0133] Example 21 Encapsulation efficiency detection

[0134] The concentration of the main component of this product was detected by high performance liquid chromatography. The encapsulation efficiency was calculated according to the following formula, and the results are shown in Table 21;

[0135]

[0136] Where: C 总 is the total concentration of the main components, C 游离 is the concentration of the main component.

[0137] Table 21 Encapsulation efficiency test results of Y-3 pharmaceutical composition for injection prepared in Example

[0138] Example Encapsulation rate% Example 1 99.1 Example 2 99.3 Example 3 99.5 Example 4 99.3 Example 5 99.2 Example 6 99.4 Example 7 99.4 Example 8 99.0 Example 9 99.1 Example 10 99.4 Embodiment 11 99.1 Example 12 99.3 Embodiment 13 99.8 Embodiment 14 99.6 Embodiment 15 99.7 Example 16 99.3 Embodiment 17 99.5 Embodiment 18 99.4

[0139] In summary, the Y-3 pharmaceutical composition for injection provided by the present invention has the following beneficial effects:

[0140] (1) Effectively improve the solubility of Y-3; (2) Reduce the free drug concentration of Y-3; (3) The preparation process is simple.

[0141] The above embodiments are only used to help understand the method and core idea of ​​the present invention. It should be noted that, for those skilled in the art, several improvements and modifications can be made to the present invention without departing from the principles of the present invention, and these improvements and modifications also fall within the scope of protection of the claims of the present invention.

[0142] The above description of the disclosed embodiments enables one skilled in the art to implement or use the present invention. Various modifications to these embodiments will be apparent to one skilled in the art, and the general principles defined herein may be implemented in other embodiments without departing from the spirit or scope of the present invention. Therefore, the present invention will not be limited to the embodiments shown herein, but rather to the widest scope consistent with the principles and novel features disclosed herein.

Claims

1. A Y-3 pharmaceutical composition for injection, comprising Y-3, hydroxypropyl-β-cyclodextrin, mannitol and Tween 80.

2. The Y-3 pharmaceutical composition for injection according to claim 1, characterized in that The content of the Y-3 is 0.1-10 mg / ml, the content of the hydroxypropyl-β-cyclodextrin is 1-60 wt %, the content of the mannitol is 0.1-10 wt %, and the content of the Tween 80 is 0.01-2 wt %.

3. The Y-3 pharmaceutical composition for injection according to claim 1 or 2, characterized in that: The content of the Y-3 is 0.1-10 mg / ml, the content of the hydroxypropyl-β-cyclodextrin is 10-50 wt %, the content of the mannitol is 1-7 wt %, and the content of the Tween 80 is 0.1-1 wt %.

4. The Y-3 pharmaceutical composition for injection according to claims 1 to 3, characterized in that: The Y-3 pharmaceutical composition for injection also includes a pharmaceutically acceptable excipient, wherein the excipient is a pH regulator, and the pH regulator is hydrochloric acid or sodium hydroxide.

5. The Y-3 pharmaceutical composition for injection according to claims 1 to 4, characterized in that: The auxiliary material comprises a freeze-drying protective agent, and the freeze-drying protective agent is trehalose, sucrose, mannitol or sorbitol.

6. A method for preparing the Y-3 pharmaceutical composition for injection according to claims 1 to 5, comprising: Hydroxypropyl-β-cyclodextrin is dissolved in a solvent, Tween 80 and mannitol are added, Y-3 is added after the solution is clear, and the solution is dissolved by stirring or high shearing, and the pH is adjusted and freeze-dried to obtain a Y-3 pharmaceutical composition for injection.

7. The preparation method according to claim 6, characterized in that: The pH value of the Y-3 pharmaceutical composition for injection is 6.5-9.

5.

8. The preparation method according to claim 6, characterized in that: The encapsulation rate of the Y-3 pharmaceutical composition for injection is greater than 90%.

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